HLA genes are the most polymorphic genes in the human genome. Knowledge about HLA polymorphism in relation to possible peptide-based, T-cell- restricted vaccination protocols is important for understanding the physiology of T-cell recognition and to improve strategies of T-cell antigen-specific vaccination. During the last year the HLA laboratory has developed and perfected techniques for high-resolution typing of HLA class I and class II molecules using polymerase chain reaction (PCR) techniques and comparing the yield and accuracy of information to other techniques, which include directed heteroduplex analysis and automated sequencing of genomic DNA. Preliminary results suggest that a combination of these techniques will allow more efficient and more accurate typing in support of peptide-based vaccination protocols presently being developed at different Institutes at NIH. Furthermore, the HLA laboratory has been involved in the development of a comprehensive method for typing T-cell receptors (TCR) based on Vb-specific, PCR-based amplification in association with directed heteroduplex analysis, for purposes of screening for TCR clonality as well as direct sequencing using automated techniques for further characterization of TCR of specific functional or clinical interest. In the future, these techniques will be utilized for the immunologic monitoring of patients undergoing peptide-based vaccination with the purpose of analyzing the in vivo expansion of various relevant T-cell populations in the peripheral circulation as well as in the area of specific pathologic interest. The ultimate goal will be to identify the steps occurring in response to T-cell antigen-specific vaccination and their correlation with clinical response.